Results after surgery in undifferentiated large cell carcinoma of the lung: the role of neuroendocrine expression.
OBJECTIVE
The objective of this study was to define the incidence of light microscopically undifferentiated large cell carcinomas, to analyze tumor stages, types of resections necessary and postsurgical survival. Additionally we tried to evaluate whether or not neuroendocrine expression influences the biological behavior of these tumors.


METHODS
Light microscopic specimens of 105 patients having undergone surgery for undifferentiated large cell carcinoma were reviewed following the 1981 WHO criteria. Fifty eight cases were excluded because elements of adeno- or squamous cell carcinoma, neuroendocrine or combined patterns of histological differentiation were observed. The remaining 47 cases of pure undifferentiated large cell carcinoma were evaluated immunohistochemically for neuroendocrine differentiation using a combination of the markers neuron specific enolase, synaptophysin and chromogranin A. The hospital charts of the patients were analyzed retrospectively recording tumor stage, operative procedure, postoperative complications, postoperative adjuvant treatment procedures, actual tumor state and survival time.


RESULTS
Thirteen patients (27.7%) had postsurgical tumor stage I, 5 (10.6%) stage II, 15 (31.9%) stage IIIA, 9 (19.1%) stage IIIB, and 5 (10.6%) stage IV. In 46 of 47 patients resections of lung parenchyma were performed (wedge resection n = 5, segmental resection n = 1, lobectomy n = 27, bilobectomy n = 3, pneumonectomy n = 10), in 6 patients combined with broncho- and/or angioplastic procedures. At the time of chart review 20 (42.5%) patients were still alive. The cause of death in the remaining patients was recurrent lung cancer in the majority of cases (24 or 92.30%). The overall mean survival of the 46 patients undergoing parenchymal resections was 19 months, the 3-year survival rate 31.7%. The immunohistochemical examination demonstrated expression of neuron specific enolase in 15 cases. Synaptophysin and chromogranin A were not detected in any case. For these 15 patients the mean survival was 25.6 months (+/- 4.3) and the 1-year survival rate 67% (confidence interval 43-91%) compared to 13.8 (+/- 2.1) months and 33.5% (confidence interval 15.3-51.7%) in the remainder. The difference was not significant (P = 0.06).


CONCLUSIONS
The light microscopic diagnosis of undifferentiated large cell carcinoma revealed to be subject to considerable interobserver variability. Undifferentiated large cell carcinoma takes a more unfavorable clinical course than other non-small cell carcinomas. Despite lack of statistical significance, expression of neuron specific enolase appeared to be associated with less aggressive biological behavior of the respective neoplasms. Immunohistochemical evaluation of undifferentiated large cell carcinomas using a combination of neuron specific enolase, chromogranin A, and synaptophysin did not provide more therapeutically relevant information than that obtained by light microscopic assessment.
Wertzel
H
H
Department of Thoracic Surgery, University Hospital of Freiburg, Germany. Wertzel@chll.ukl.uni-Freiburg.de
Grahmann
P R
PR
Bansbach
S
S
Lange
W
W
Hasse
J
J
Böhm
N
N
D014408:Biomarkers, Tumor / Q000032:analysis*; D002289:Carcinoma, Non-Small-Cell Lung / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D053379:Chromogranin A; D002864:Chromogranins / Q000032:analysis*; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000401:mortality / Q000473:pathology / Q000601:surgery*; D015588:Observer Variation; D010751:Phosphopyruvate Hydratase / Q000032:analysis*; D011013:Pneumonectomy; D011183:Postoperative Complications; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate; D016708:Synaptophysin / Q000032:analysis*
D014408:Biomarkers, Tumor; D053379:Chromogranin A; D002864:Chromogranins; D016708:Synaptophysin; D010751:Phosphopyruvate Hydratase